Faculty Forum Online, Alumni Edition: The Addicted Brain

Faculty Forum Online, Alumni Edition: The Addicted Brain


Hi. I’m Whitney Espich, the CEO
of the MIT Alumni Association, and I hope you enjoy this
digital production created for alumni and friends like you. OK. Well, good afternoon and welcome
to the MIT faculty forum. I’m Evan Morris and I’ll
serve as the moderator today. For background, I’m a
biomedical engineer by training, and these days, I’m a
professor of radiology and biomedical
engineering at Yale. As you’ll hear a
little bit later, I study the brains of people
addicted to drugs using brain imaging technologies. And what’s nice about this
forum that we have today is that my fellow
panelists and I span the spectrum
of research, from basic to applied
translational with humans, to clinical applications. As a reminder, we welcome your
questions during this chat. For MIT alumni joining
via Zoom, please use the Q&A feature
found on your toolbar. For all others
listening on YouTube, you may add your questions
to the comments field. We also encourage you to
tweet using #MITbetterworld. We’ll get to as many
questions as we can. Today, we hear from
our three experts. Well, two experts and me. And we’re going to start
with Dr. Nune Martiros, who’s currently a postdoctoral
fellow at Harvard University. Hello, everyone. I hope you can see me. So I’m a postdoctoral
researcher at Harvard here in the Murthy Lab. And before that, I
was a graduate student in Ann Graybiel’s lab at MIT
studying basal ganglia circuits and how they contribute
to habitual behaviors. So I’m just going to tell you a
little bit today about the work that I did in Ann’s lab. And let’s see if I
can get some slides. OK. So I’m going to
do a share screen and I’m going to go to you. So let me know if this is
problem if you can’t see it. What I wanted to talk about is
that whether you may realize it or not, most of our life
is made up of habitual action sequences, and most of the
time, this is a very good thing. So things like making
your coffee in the morning or trying your shoelaces
or, for example, riding your bike
from your apartment to your lab every day. We do these actions in a
very stereotyped manner and this way, we can kind
of allow our attention to go to more novel tasks
that are more difficult. For example, writing
our dissertation, which is not habitual at
all and it requires a lot of mental resources. So what actually
happens when behaviors go from you first learning
them to them becoming habitual? Behaviors start off
being deliberated, requiring attention, being
quite slow and variable. So you can try different
options to see what works best, and be responsive to
changes in the outcome. So if your context changes,
if your behavior is not producing the result you wanted,
you can easily change it. But once the same
behavior becomes habitual, it becomes reflexive,
requires minimal attention. It’s fast and stereotyped. You do it the same
way each time and it becomes unresponsive to changes
in the environment, which can be a bad thing when you need
to change the behavior in order to adapt to new environments
or requirements. And one other special
property of habitual behaviors is that oftentimes,
they are composed of multiple different
steps, which are chunked together
so as to create a single unit of behavior. So for example, when
you’re brushing your teeth, you have multiple steps
involved in doing that. But once you learn to
do that, you kind of think of it as a
single action sequence. And this chunking
phenomenon is what I was really interested
in studying in grad school and I chose to focus on the
region of the basal ganglia, which is called the
dorsolateral striatum, which we know is extremely important
for habitual behaviors. And we know this
for many reasons, but partially because when this
area of the brain is damaged, animals have trouble
transitioning from this deliberative
slow stage I was talking about from
the initial stage of habit learning to the later
stage of habit learning. So what I wanted
to do is figure out what’s actually going
on in the basal ganglia and the striatum that
facilitates this learning of habitual behaviors. So in order to
study this, I taught rats a basic habitual
action sequence. So this would be kind
of the analog of you typing the password into
your computer every day or typing in your
ATM code or something like that, where you
do it so many times it just happens
by itself kind of. So for the rats, what
they had to learn is to press a specific
sequence of three levers. And so, for example,
in this rat, they had to press the first
lever, then the second lever, then the first
lever again in order to get their
chocolate milk reward. And if they did any other
sequence of presses, then they wouldn’t
get the reward. And so what I did is I taught
a bunch of different rats to do a whole bunch
of different sequences to see whether I see neuronal
activity in the striatum that has to do with the development
of a chunked habitual action sequence. And you can see that the
rats did learn to do this. And not only did
they learn to do it, but they also exhibited
certain behaviors that made us think that they
were really developing a habit. So for example, they would
follow stereotyped movement trajectories. Here you can see
the rat’s head is moving in the same
way trial to trial when they’re doing
their sequence. Importantly, each rat
did it differently. So they were assigned
different sequences and they also developed
different ways of doing it, so they developed their
own special little habit that was different
from animal to animal. So what was going on with
the neurons in this habit related area of the striatum? Well, what the neurons
were doing was that– so here, I’ll just explain
this chart a little bit. Each row in this color
plot is a single rat, and you can see here on the left
which sequence they learned. Each of the black lines
are the three lever presses that they did, and then
the color of the color plot indicates how active the
neurons were at that time. And what you can see is
that across the rats, regardless of which
sequence they learned and which movement they were
doing, the neurons in this area were active around the start of
the sequence that the rat had learned and around the
end of the sequence that the rat had learned. And we think, in combination
with the fact that we saw the same kind of start and end
activation in rats that were doing a totally different
habitual behavior, rats that were running
down a t-shaped maze– and again, these
neurons were active at the start of the maze run
and at the end of the maze run. We think that probably what
these neurons are doing is responding
basically demarcating habitual behavioral units that
the animals have developed. And we did a lot of things to
rule out other explanations like movement. We found that this doesn’t
happen when the rats are doing the wrong sequence
that they never learned that they weren’t rewarded for. And also what was
interesting, is there was a different kind of
neuron, an interneuron, which is sort of a locally modulating
neuron that modulates the principal neurons,
that were doing the opposite pattern here. So what you can see here
is that the main neurons were peeking in activity at the
start and end of the sequence. The red plot here shows what
these interneurons were doing. So they were doing
the opposite pattern, potentially keeping down the
activity of those projection neurons while the
animal was actually performing the sequence. And what was kind of fun to
see was that in the cases where the rats messed up– so for example, here
what I’m showing are the cases in which they
started off doing the first two presses correctly and after
that, the third press, they messed up. And what happened is that
you see this activity. The start activity
peak is there, and then the middle activity
peak in the interneurons is there, but then when you
get to the last incorrect press that they did, the end
activity peak never comes and then the interneurons
are still kind of going like, oh, I guess we’re not done yet. So this neuronal activity
in this part of the brain was really reflecting
specifically this sort of abstract concept
of whether the rats were performing a habitual
action sequence that they had been
rewarded on before. What does this mean? What can we make out of
this neuronal activity? Well, we know that learning and
selecting behavioral repertoire is a fundamental function
of the nervous system, and we also know that
over or under expression of habitual behaviors
is critically detrimental to quality of life. If you’re unable to develop
these habitual behaviors and every single little thing
you do in your daily life, you have to think about
every step you’re doing, that’s going to be
really difficult. Whereas if you’re
too habitual, you’re doing these
compulsive behaviors. For example, like in
obsessive compulsive disorder. Now this is really
maladaptive because you’re unable to reallocate and sort of
adjust your behavior as needed in order to adapt. Similarly, in drug
addiction, which is obviously the main topic of this
forum, a certain trigger can cause the cascade of some
habitual behaviors, which lead to the drug taking, and
it’s a self-reinforcing cycle. So addiction is also very
much another disorder in which there’s over expression
of habitual behavior. Whereas, for example,
in Parkinson’s disease, there’s a loss of learned motor
action sequences that people had previously in their life
that they become unable to do once they develop Parkinson’s. So that’s it for my little talk. Let me know if you have
questions about that later. I’m going to stop
sharing my slides here. OK. It’s OK? Good. Back to the normal view? OK. So I’m going to try to pick up
a little bit where Nune left off by showing some work that we’re
doing at Yale on experiments on people. And the first thing
I need to do is be able to share my screen with
you so you can see what I see. OK. And that should happen shortly. OK. Hold on a moment. Sorry for the delay. I’m just going back to the– OK. So it’s always good form,
when you’re a professor, to start with acknowledging
all of your students, which I do on my first slide. So all of the people on the
left were either students or postdocs whose
work contributed to what I’m going to show
you, and in exchange, we gave them a PhD. OK. So this is a design
of a study that we do with human subjects
who are addicted smokers, and we study them with
PET brain imaging. And important things
to know for the purpose of this little discussion
is that our smokers come in and they’re abstinent
from the night before, and so presumably, they’re
craving their cigarette. We place them on a PET scanner,
which is indicated down on the left, and we inject
them with a radioactive tracer, which is necessary to
perform the PET study. And at some point
into the study– actually 35 minutes into what
is a 90 minute scan session– they smoke one of
their own cigarettes. They give themselves
the cigarette. And so for those of you
who are addiction experts, this is self-administration. And we create the
images over time and we look for the dopamine
response to their cigarettes. Dopamine is the neurotransmitter
in the brain that is encoding reward, among other things. And we look specifically
in the striatum, which is an area of the brain
that the previous speaker spoke about. And if you wanted to
actually observe this study, it would look
something like this if you were looking into
the PET suite at Yale from the control room. And you see that we’re
monitoring head motion. There’s a picture of
me when I had hair. We’re filtering away
the secondhand smoke so that the techs
are not injured and the person in
the scanner is being scanned and about to smoke. Now, on this slide,
this shows you the most important thing, of
course, about doing research, is the graduate student. And in this particular
case, the graduate student is doing a very, very important
job, which is not only lighting the
cigarette, what you see in the middle of the picture,
but catching the ashes so that we don’t burn
up the subjects. OK. Here’s some real data that
derives from those experiments. And this is going to
go by pretty quickly, so I’ll show you twice. This is the same
person, the brain of the same person smoking
once on the top row and then coming back
another day not smoking. So just to show you
what we actually derive from these experiments
and the mathematical modeling that goes next, let me
play the video a few times. It goes by very quickly. You should have noticed
some burst of activity in the striatum, which is
here on these contiguous slices in the brain
of the subject, but nothing at rest when
they’re not smoking. So let’s look at it briefly. I’m sorry. Let’s look at it
briefly again just to convince you that we’re
actually picking something up, which for reasons I
can’t explain right now, attribute to dopamine activity. OK. There we go. One more time, the
burst of activity in the ventral striatum of the
person when they’re smoking, but not when they’re
doing nothing. All right. Now, this is just
for MIT alumni who may be asking at this
point, well, what’s the engineering in this? There’s a lot of physics
impact and there’s a lot of radiochemistry,
but for me, this is the contribution that my
students and my lab and I make, which is that the
models that used to be used to analyze
the data that we generate were previously assuming that
dopamine was at steady state, but the models that we
contributed to the field are in a sense tuned to the
frequency of brief cigarette induced dopamine events. They’re not quite as fast as I
showed them, which is seconds. They happen over minutes. But since they only
allotted me my seven minutes during this podcast,
I showed it to you quickly. So now, here’s the
heart of the matter. If you look at the bottom
row– and I’ll show it twice– this is a male smoker. I’ll come back to it. And now the female smoker is
being shown on the top row. Let me replay it
because I think you’ll be able to distinguish the
difference that we started to see as a consistent
pattern when we compared male to female smokers. I’m going to play
the bottom row. Look at the bottom row
of contiguous slices in the brain of
this male smoker. And notice that here, in
the right ventral striatum, there was dopamine response. Now, if we look again
at the female smoker by looking at the
top row, you’ll notice that a little
later in her scan, she responds in the
dorsal striatum. And this was something
that had been– there is evidence
for sex differences, but let me try to explain
why this is important and to tie it back to
the previous speaker, who spoke about habit. So what do we know
that’s different about male and female smokers? Well, for one thing, men
are reinforced by nicotine. And interestingly
enough, it turns out that they are about
1 and 1/2 times more likely than women
to stay abstinent on nicotine replacement therapy
like the nicotine patch, and this implicates
the ventral striatum. Whereas women smoke for other
reasons, such as social reasons and cues, and in
particular, focus on habit. And they turn out to be less
sensitive to the nicotine level in their
cigarettes than men are. This in turn implicates
the dorsal striatum, which is just the
type of difference that we were seeing between
our male and female smokers. So there was some
consistency to what we saw, and so now we’re engaged in
a much larger study looking at the effects of addiction,
in particular still smoking, on the brain. I think of it as a signature,
a John Hancock of addiction. And we’re also looking for
the effect of treatments, including nicotine replacement–
this is the right half of the slide– on that signature of
addiction, and in particular, we’re searching
for sex differences in the alteration of the
addiction signature caused by treatment. OK? So I’m going to leave
it there and give way to our third speaker, who
is Professor Amy Meadows at the University of Kentucky. Let me stop sharing my screen
so that Amy can proceed. Hold on a moment please. OK. Sorry. Having a little trouble here. Screen sharing. OK. I think Amy should be
able to proceed now. Thank you so much. So I’m going to talk
just a little bit about the clinical application. And I’ll you a little
bit about my background. So like everyone here, I
went to MIT for undergrad. I was a brain and
cognitive science major. I went on to get my
MD, so I am going to talk about the clinical
perspective of addictions. And specifically, I am a child
and adolescent psychiatrist and a pediatrician. And so I’m going to talk about
addiction in adolescence. So after I finished
my fellowship, I returned home,
which is to Kentucky. So I’m at the
University of Kentucky. And as many people
may know, I am right in the middle
of the Appalachia, which is currently the heart
of the opioid epidemic. If you look at
heat maps for where addiction, and specifically
opiate addictions, are the most prevalent
in the United States, kind of right up and down
the Appalachian Mountains tends to be one of the places
where there is the most. So my initial interests
were in early life adversity and childhood
trauma and how that shaped different behaviors. And specifically, when I
was getting my MD at Yale, I was doing neuroimaging looking
at early life adversity, child maltreatment, and the
prefrontal cortex. And so a lot of
what I do now also relates to the
prefrontal cortex. So instead of talking
about the striata, I’m going to talk a
little bit about how our executive functions can
modulate addictive behaviors. So we know that people do things
that aren’t good for them. They smoke, they don’t take
medications that are effective, and a lot of times, people
do things under stress. So there’s a very
complicated relationship between stress and behaviors,
especially addictive behaviors. We know that adolescents have
a high rate of experimentation with substances. Current statistics show
about 4% of US seniors have experimented with
opiates, for instance. Most commonly, they
are medications that are available in their
home or from their friends like hydrocodone,
oxycodone, tramadol. And medical use
of opiates in kids highly correlates to subsequent
non-medical use of opiates. Interestingly, the pattern
has somewhat changed. In the early 2000s,
more kids were using to get high, whereas a
lot of what is described now is that adolescents
use to relieve tension and to relieve negative
affective states. But there are some
good numbers that are coming out that use
of opiates has decreased. Although, unfortunately, rates
of things like emergency room visits and overdoses have
continued to increase. Now, the adolescent brain
is pretty interesting. We’ve talked a little
bit about the reward circuitry and dopamine
being very reinforcing. But what’s fortunate is that the
prefrontal cortex can modulate often the effects of
dopamine release– that someone knows
that they have to work, that they
are planning, and have reasons to not use or not
follow habitual behaviors. However, the prefrontal
cortex in adolescence is undergoing a period
of extreme change, so there is synaptic
change, they’re undergoing dendritic
process pruning, neuronal membrane
synthesis, and myelination, which is really important. Now, this becomes important
because you combine a period of experimentation
with less ability to modulate behavior
and you become what’s known as all
drive and no brakes. So this is a high risk
period for substance use, and we know that when you use
substances earlier in life, that that is a higher risk
for problem use as you go on. Now, I mentioned that my
specific area of interest is stress, and especially
early life adversity, so a concept known as
adverse childhood experiences or ACEs, which is not
just child maltreatment, but a broader
category of household dysfunction during childhood. And about 50% of the population
attributable risk of drug abuse is relatable back
to early adversity, so this is something that
happens pretty frequently. And if you look at community
samples, in some communities, the comorbid risk of
post-traumatic stress disorder and substance use in
adolescents is as high as 20%, so one in five kids have
both PTSD and substance use disorders. And that’s here in the
United States, unfortunately. Now, what’s really
interesting is that if you look at animal
models that, for instance, exposure to shocks increases the
reinforcing nature of opiates, and that relates to kids saying
that they’re using opiates to relieve tension, so
similar to what rats will do. We also know that
the stress state just allows less modulation
of the reward pathway. So there’s increased sensitivity
to environmental cues, rather than being
able to decrease the habitual
addictive responses. So I’ll just briefly
end on talking about my research,
which I’m looking at how adverse childhood
experiences affect health risk behaviors. So that includes
addiction, but also perception of risk
and planning, as well as impulse control,
which all relates back to those executive functions. And what’s been
found is that there is a dose response to the
amount of early life adversity that you have to your risk
for a lot of these things. So to your risk for cigarette
smoking, your risk of opioid use disorders. And although some of
this is replication, we’re also trying
to use technology to ask these questions
in a novel way. So there’s some
indications that teenagers will be more truthful when we’re
asking via technology using iPads or using computers,
rather than asking in person, and using kind of ecological
momentary assessment, so day to day assessments of
mood and stress states and how that relates to
some of these risk behaviors that they may be engaging in. And really the ultimate goal is
to ensure that we’re not just addressing the substance use,
but also the predisposing factors that may cause
somebody to be at risk for an addictive behavior. So I apologize for not
having a PowerPoint, but hopefully I kind of
conveyed that overview of what I’m interested in
and what we’re doing here. I’d be happy to
answer questions, too. Thank you very much. Let’s see if we’ve
received any questions yet from the participants. OK. So we do have a question
for Amy and it asks, how do you measure
household dysfunction in an objective way? So the short response is
that we’re asking humans to report on their
experiences, so really we are using validated
measures of something called an average childhood
experiences scale where people are reporting on
their own early life traumas as our marker. And that’s been used in lots and
lots of epidemiologic studies, as well as in smaller
studies, to be validated. I see. Thank you. OK. Let’s see if we have any other
questions from the audience. They’re running to their
dictionaries and encyclopedias first to formulate their
questions, apparently. Well, maybe if either
of you can tell us perhaps more about
anything that you learned at MIT that related to
your professional choice and the work that
you’re doing now that might be of
interest to the audience. Is that possible? Evan, I think that there is
a question for you that says, could you elaborate
on some results after treatment
for men and women? Sure. If you have them. Yeah. Thank you. OK. Great. Thank you. So I would say that
right now, we’ve been studying in our
follow up study that was sort of indicated in my
last slide for a few years, and we are preliminarily
finding differences in the dopamine response– I should say sex differences– in the effect of nicotine
replacement on what we think is the standard male versus
female response to smoking. But that’s preliminary and
it’s not published yet, so don’t go out
and bet the house, but that’s what we’re
finding and it’s consistent with our hypothesis. So what we hope is that we’re
finding sort of the actions in the brain that determine
the difference in response to nicotine replacement
that men and women see. OK. So it looks like we have
a few other questions. Let’s see if we
can divvy them up. So there’s a question here. It’s not clear. Maybe it’s for Amy. Are these brain and
behavioral patterns independent of the
nature of addiction? That is to say,
smoking versus alcohol versus illicit substances. And then there’s an ask for
references, which maybe we can provide later online. I would say for me,
it’s certainly the case that many addictive
substances have been studied with PET
imaging and typically, we understand that the
dopamine response to all of these addictive
substances is quite similar because
ultimately, whether it’s nicotine or alcohol,
the downstream effect is to funnel through
the dopamine system to encode reward. And we are with our technology
studying other addictions. Maybe one of the
other panelists would like to say something, as well. I would just like to amplify
that all of the substances, to a greater or lesser degree,
are activating the reward or motivation pathway. We do know that there is
variability between how addictive certain
substances are. For instance, if you
smoke one cigarette, you may be at less
risk of addiction than if you do
one hit of heroin, but the underlying brain
pathway is very similar. OK. Finally, our participants have
thrown off their inhibitions, so they’ve disinhibited their
prefrontal cortex, perhaps, and they’ve sent us
a slew of questions. So I’m just going to go through
and we’ll try to get to as many as we can. Eric Sadler asks, I
was hoping to hear more about neurological
changes from substance use. And I can say from an
imaging standpoint, there are many drugs of
abuse that are known– well, are believed
to, I should say– diminish the number of dopamine
receptors and other brain receptors. I think it’s not entirely
clear yet whether people are born that way, or it’s
a result of substance abuse. That’s what I can contribute. Does anybody else want
to jump in on that one? OK. Maybe we’ll go to the next one. So Miko asks, what are
some effective ways to snap out of addiction? That sounds like a
clinical question. Sure. I can take that. So I think that there are a
lot of different models for how to treat addictions. One of the big
factors is motivation, and so a lot of the
evidence based practices about addictions
treatments are focused on how to kind of mobilize
people’s own reasons for wanting to change and their
own kind of internal motivation to snap out, in the question’s
words, of an addiction. There are lots of
effective treatments, including cognitive
behavioral therapies, mindfulness-based therapies. For things like
nicotine and opiates, there are agonist
therapies where you have a replacement for
the addictive substance. And there are also some
psychopharmacological treatments of addictions
that have shown promise for certain substances. OK. Now here’s one I’m not
sure what the answer is. Let’s see what we know. So Nazir asks, what
about sexual addiction, and specifically it sounds
like he or she is asking, are there differences
between men and women? I don’t actually know. I’m guessing that sex
addiction is also dopaminergic. I don’t know of any
studies in my field. There are certainly
studies about gambling, which is dopaminergic. Maybe one of the two of you
has something else to add. No? It’s not my area of expertise. OK. All right. Let’s move on. Sorry. Once someone acquires
a dopamine sensitivity to an addictive
behavior, can this ever be reversed or is the
brain permanently changed? So I should know that
from imaging studies, but I can’t say that
I do know the answer. I’m hoping maybe one of my
colleagues is on the line and can answer. Anybody else? My understanding is that
there are certain changes that I wouldn’t necessarily
say are permanent, but that are long lasting, even
after the addictive behavior itself has ceased. So even after, for
instance, you’re abstinent from a
substance of abuse, there are some neurobiological
changes that remain and that you may always be– maybe not always,
but for a long time may be– vulnerable to
certain cues of the substance. So seeing somebody
else smoke or when you’re going through a
particularly stressful period of life, you may be more
likely to revert back to substance use. All right. OK. Thank you. I know that there
are certainly– I would call it, I guess,
not necessarily dopamine sensitivity, but the flip
side, which is tolerance. In many cases, drug
addictions cause diminished dopaminergic
responses to drugs. And I think that
that’s long lasting. So here’s a question
from Bob, which goes back to a previous question maybe,
and it’s clinical, again, I think, which is how does one
interrupt the addictive brain thread, from cigarettes
to alcohol to food? Maybe the question is
more about substituting one addiction for another. All I can say is that I know
from recruiting our subjects– I also study alcohol
addiction– oftentimes these two things
go hand-in-hand. Does anybody have
another comment? OK. And I guess this one’s
for me specifically. I’m being asked, would we
expect gender differences, such as what I was
alluding to with smoking, would be similar
for adolescents? And that’s a very good question. And unfortunately, in my case,
I have a methodological answer, which is we’re not allowed
ethically to do PET imaging– that’s my get out of
jail free answer– because we inject radioactivity. But certainly at some
point, unless these things are inbred– inborn, I should say. Excuse me. We would have to expect
a sort of divergence in the development of addiction. So I’m guessing–
don’t hold me to it– that at some point during
the course of addiction, there is a divergence between
men and women in their response to addictive substances. And I think I can actually
say, from what I recall, that women proceed more
rapidly to the habitual stage of addiction, at
least with smoking. Again, my colleague was not on
the line who is the cigarette smoking expert, so I apologize. This is a basic science
question for Nune. Do you have any ideas
or data about how to break a chunked action? Hi. OK. I have ideas about it. I’m not sure how much
has really been– I think it’s a bit harder
to study in animal models, but I think in people,
usually some good strategies are things like, basically
if there’s some trigger that causes you to start
some chain of actions, then perhaps try to substitute
a new action in the second step or in the third step and
then kind of repeat it many times over so that it
kind of interferes maybe with the circuits that are
reinforcing the existing chunked action sequence
that you do have. Another option would
be to just avoid the trigger in the first place. So this also, I think,
works for drug addiction, is to kind of try to unlearn the
behavior by kind of setting up circumstances in which you are
not triggered to perform it for a long time, after which
that maybe it will be easier to kind of decompose that
behavior and alter it. So I think substitution
and avoidance are both good options,
but substitution was something that is good, not
with another kind of behavior that you don’t want to
be doing, obviously, is the best strategy. OK. And here’s a nice
follow up question from Patti Newbold, who
was obviously listening and synthesizing what
everyone was saying, because she asks
for Nune, what role does dopamine play in chunking
of habitual behaviors, if any? Yes. So we do think dopamine plays
an important role in two ways. One is that we think that
perhaps dopamine is really important for creating the
beginning and end neuronal activity that I showed
you in the striatum. So some reasons we
have for thinking that are that some people have
found similar kinds of activity in dopamine areas of the
brain, which send connections to the area of the striatum
that I was talking about, and also because dopamine can
cause connections between brain areas. So for example, the
input from cortical areas to the striatum,
which may be becoming shaped during the process
of the habit learning. This can be modulated
by dopamine. And then on top of
that, what can happen is that usually, the
behaviors that become chunked are the ones that
are reinforced. And so there is an interaction
between ventral striatum and dorsal striatum
where ventral striatum is sort of participating in
reinforcement learning, and then the behaviors which
lead up to that reinforcement may be encoded and chunked
by dorsal striatum. So yes. We do think it plays
a big role, for sure. OK. Thank you. Amy, I think this question is
for you from Eileen Hopkins. And she says, regarding
teaching replacement behaviors to the addicted, which behaviors
can one teach or recommend to the addicted that can
compete with opioids to relieve the stress they are attempting
to medicate or to alleviate? So I’d say that nothing can
compete with an opioid high. The way people
subjectively describe, especially the first
time that they use, is that it is a
transcendent experience. People who are predisposed
to addiction, especially. So really there is nothing. We can do medication agonist
treatment that can sometimes help to hit some of
the same receptors, but it doesn’t have the same
experience of getting high. And so really a lot of
times what the treatment is is learning how to manage stress
and to accept negative emotions and distress, rather than trying
to bury it with substances. So oftentimes, it’s not that
we are having competing– because nothing would
compare with opiates– but rather to
promote acceptance. OK. Thank you. I think I have three
questions that I can lump or chunk,
as it were, together, having to do with a nicotine
replacement and other means of delivering nicotine and
possibly men who do or do not respond to nicotine therapy. So I’m just going to give
a generalized answer, which is to say that despite what
we’re finding preliminarily, I would not go so far– and
I’m also not a clinician. I would not go so far as to say
that nicotine replacement does not work for women. I think you have to think about
these things as overlapping populations. So we’re going to
learn, we hope, what the differences
might be in the response, and ultimately,
perhaps that will lead to the development
of new treatments that are better for people who
don’t respond to the existing ones, such as
nicotine replacement. But I certainly can’t
say categorically that all women should throw
away their nicotine patches, particularly if
it’s helping them. Similarly, we personally–
my group, my students, and my colleagues– are very
interested in also studying the response to other now
popular, gaining popularity methods of delivering
nicotine like vaping, but I have nothing
to say about it yet. And maybe I’ll leave it there. Here’s a technical one, and
then I’ll give over the floor. Are SPECT scans as
useful as PET scans to visualize various
brain structures regarding addictions? So, yes, there’s a very
big role for SPECT. Oftentimes, SPECT does not have
the same spatial resolution as PET. But there are practical
advantages to SPECT, such as the use of
longer lived isotopes. So what we do in our
PET center at Yale is very much in the
realm of research. And SPECT, which uses
longer lived isotopes, is much more practical for
circumstances in the hospital where you don’t have the luxury
of controlling the patient’s time, but you can wait longer
with the tracer at the ready. I think I’ll leave it at that. And then there’s a
thank you to Amy, who I guess was very popular
with some of our viewers. I’m not surprised. OK. Should we take a
couple more questions? Let’s do this, because we’re
getting quite a number of them. Maybe some of them we’re going
to try to respond in writing, but let’s see if we– OK. This sounds like another
clinical question. Well, two things. How important are genetic
predispositions to addiction, and our faith based addiction
therapies such as AA more effective
than programs that do not rely on calling
upon one’s higher power? Would you like to
address either of those– genetic predisposition
or treatments? Yeah. I can definitely start with
genetic predisposition. The bottom line is that
substance addictions are one of the most
heritable diseases out there, as so or more than
things like type 2 diabetes, which we think of
as very heritable. But if you look at the variance
between why one person gets it and why another person
does not, a large portion of that is due to
genetic susceptibility to addiction and addictive
behavior, which I think just reinforces that these are
brain based disorders. Even though a lot of
times our culture frames addictions as something
that is a lifestyle choice, these are very much related
to underlying behavioral and genetic susceptibilities. OK. Thank you very much. There are a number of questions
about other neurotransmitter systems. I don’t think any
of us want to leave this forum with the
message that dopamine is the only important
neurotransmitter, but certainly
these things funnel through the dopamine system. I can say briefly
and only indirectly in response to another
question that we’re also studying systems like the
opioid receptor system, not surprisingly, these days. And in my own lab, we have
found some sex differences in kappa opioid receptors. And I think it remains
to be seen what other sex differences we’ll see in
other neuroreceptor systems and in other addictions. Yeah. And I would also add to that
that, for example, a big topic of research recently
in the basal ganglia has been on the interaction
between acetylcholine and dopamine. The same receptors
that smoking acts upon are really critical,
as it turns out, for dopamine to have its
effect on the synapses and the basal ganglia. And they facilitate that
effect or modulate it in different ways. So for sure there’s lots of
important neurotransmitters that interact with dopamine. OK. I’m sorry. We still have
questions, but I don’t think we’re going to
get to all of them. So unless there’s a
burning last statement, perhaps I’ll just wrap up. OK? So I need to say that on behalf
of the Alumni Association, I want to thank everyone
for tuning into this faculty forum online. Thanks very much to
the expert panelists from Harvard and
Kentucky, and it was my pleasure to join them. And we didn’t get to
all of the questions– I apologize– but we will
forward the questions to the panel. And please tweet
about today’s chat using the hashtag
MIT better world, and send follow up
questions or feedback to [email protected] Thank you again for joining us. Thanks for joining us. And for more information on how
to connect with the MIT Alumni Association, please
visit our website.

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